ABSTRACT ? STRUCTURAL BIOLOGY SHARED RESOURCE The mission of the Structural Biology Shared Resource is to advance our understanding of the molecular basis of cancer by giving Cancer Center scientists access to equipment, technology and expertise for structural and biophysical studies of biological molecules. Structural biology enables multi-scale visualization of molecular and supramolecular structure and dynamics with the ultimate goal of characterizing biological systems in their functional native states. This requires a multidisciplinary approach that spans the ranges of length and time scales effective in biology. The Core, managed by the Center, maintains state-of-the-art equipment, develops technology, provides service, and promotes collaborative activities with Cancer Center scientists. There are four central and complementary areas of structural biology: nuclear magnetic resonance (NMR), X-ray crystallography, the recently added electron cryo-microscopy and cellular tomography (cryo-EM, and ET), and the long-standing biomolecular analysis facility. These technologies are typically not available in individual Center member laboratories, owing to their expense and complexity of operation. Core equipment supporting NMR includes two 600 MHz instruments with cryoprobes, a wide bore 500 MHz spectrometer set up for solid state analysis, and a highly automated 400 MHz instrument supporting chemistry. X-ray crystallography equipment includes a robotic dispenser and two, automated imaging incubators (5 and 20), a Rigaku FRE SuperBright X-ray diffractometer with two independent beams and detectors. Cryo-EM analysis is supported by a Thermo Titan Krios with a 4Kx4K Falcon III direct electron detection device and a phase plate, as well as a Tecnai 12 Spirit G2 equipped with a 4Kx4K CCD. Finally, equipment supporting biomolecular analysis includes an analytical ultracentrifuge, DSC, UV/vis spectrometry, Fluorescence spectrophotometer, two ITC instruments, and MST. The three Ph.D.-level Core staff maintain the equipment, train users, and in the case of biomolecular analysis, provide full-service analysis. For structural biology analysis, Core users can collaborate with Core staff for smaller projects or collaborate with expert structural biology groups in the Cancer Center to pursue more complex projects. A number of such successful collaborations are described in the Research Plan. In the past 5 years, the Core was used by 16 Center labs representing all three programs, and supported 62 cancer-related publications.